DESCRIPTION (Applicant's Description): The cell cycle continues to be a focal point of biological research. This is because regulation of cell prolifera-tion is essential for the viability of all organisms and because all aspects of cellular physiology ultimately impinge on the cell cycle. Over the past 10 years, study of the cell cycle has moved from the realm of phenomenology to that of elucidation of mechanism at the molecular level. The most significant conceptual advance has been the recognition that most, if not all, cell cycle transitions are mediated by protein kinases known as cyclin-dependent kinases. This has led to an intense application of effort in the investigation of the regulation of cyclin-dependent kinases and the nature of downstream targets of cyclin-dependent kinases, both in the context of cell cycle control. Although there has been significant progress in understanding cyclin-dependent kinase control, a remaining critical question is the nature of downstream targets and how phosphorylating them promotes cell cycle transitions. Of particular interest is the relationship between cell cycle transitions, cyclin-dependent kinase activity and regulated proteolysis. Finally, an enduring mystery from the perspective of human disease is why mutations in some elements of the cell cycle control machinery, including cyclin-dependent kinases, are strongly implicated in cancer whereas others are not. The goal of a Keystone Cell Cycle Meeting is to bring together a diverse group of investigators engaged in subdisciplines of the cell cycle field in order to stimulate discussion, generate new ideas and to forge collaborative efforts, all in the interest of addressing and resolving the issues outlined above. There is no other medium-sized meeting in the US on this subject that can attract a high percentage of leading investigators in the field, thus serving as a nucleus for such a discussion.